Project Summary/Abstract: When breast-feeding is not possible, cow's milk based formulas are the preferred alternative sources of nutrition. Formula milk fed infants have strikingly more morbidity and mortality with infectious diseases as the major cause. S-IgA, lactoferrin and lysozyme in breast milk are the major antimicrobial factors. Lactoferrin and lysozyme function through nonspecific mechanisms, and S-IgA functions through both specific and nonspecific mechanisms. Therefore, it is hypothesized that baby formula supplemented with nonspecific S-IgA, lactoferrin and lysozyme will better protect the newborn against infections at the mucosal surfaces. While the proposed studies will focus on adding nonspecific S-IgA along with lactoferrin and lysozyme in formula milk to provide protection by nonspecific mechanisms, this technology can also be used to produce formula with pathogen specific S-IgA as future products. To test the hypothesis, 3 specific aims are proposed in Phase I. First, to produce formula milk with nonspecific S-IgA, lactoferrin or lysozyme or a combination of the 3. Second, to determine the in vitro antimicrobial effects of the formula with S-IgA, lactoferrin and lysozyme against Escherichia coli O18ac:K1:H7 and the gram-positive bacteria Streptococcus pneumoniae 3 and 6B. And finally, to determine the ability of the formula with S-IgA, lactoferrin and/or lysozyme to prevent binding of Escherichia coli O18ac:K1:H7 and the gram-positive bacteria Streptococcus pneumoniae 3 and 6B to human epithelial cells in culture. [unreadable] In Phase II, we will expand these studies to determine the antimicrobial effects of the most effective formulation against other microbes commonly infecting newborns. Second, we will examine the in vivo efficacy of the most effective formulation in a validated animal model. Project Narrative: Formula milk fed infants have strikingly more morbidity and mortality with infectious disease as the major cause. Secretory IgA, lactoferrin and lysozyme not present in formula milk[unreadable] but present in human milk protect against infections. The goal of these studies is to produce a liquid formulation containing secretory IgA, lactoferrin and lysozyme in a dropper bottle that can be readily added while preparing formula milk to protect the infant against common infections. [unreadable] [unreadable] [unreadable]